Safety and efficacy of underwater endoscopic mucosal resection for 10-20 mm colorectal serrated lesions (SEA CLEAR study).

BACKGROUND AND AIMS: Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater endoscopic mucosal resection (UEMR) for SLs sized 10-20 mm. METHODS: This two-center prospective observational study included patients with at least one SL sized 10-20 mm. We resected the SLs by UEMR and performed tattooing at the resection site. Surveillance colonoscopy was performed 12 months postoperatively to evaluate local recurrence. The primary outcome was the complete resection rate of UEMR, which was defined as en bloc resection with no serrated tissue in the four marginal biopsies and histologically negative margins. RESULTS: UEMR was performed for 65 SLs in 58 patients, with a median lesion size of 14 mm. The en bloc, R0 resection, and complete resection rates were 87.7% (57/65), 61.5% (40/65), and 60.0% (39/65), respectively. Adverse events included 1 (1.5%) immediate bleeding and 1 (1.5%) delayed perforation. Surveillance colonoscopy was performed in 50 patients with 57 scars, and the rates of identification for tattoos and scars were 94.7% (54/57) and 100% (57/57), respectively. The recurrence rate was 5.3% (3/57), and all three recurrent lesions were completely resected endoscopically. CONCLUSIONS: This two-center prospective study demonstrated that UEMR for SLs sized 10-20 mm was comparable to previous conventional endoscopic mucosal resection outcomes.

Multiple Gastric Neuroendocrine Tumors Associated with Long-term Use of a Proton Pump Inhibitor and a Potassium-competitive Acid Blocker.

A 52-year-old man who had been using a proton pump inhibitor (PPI) and a potassium-competitive acid blocker (P-CAB) for 14 years underwent esophagogastroduodenoscopy and was found to have three neuroendocrine tumors (NETs) in the gastric body. Following detailed examinations, parietal cell dysfunction was excluded, and the NETs did not meet the criteria for the Rindi classification types I-III. The lesions were ultimately considered to be associated with the long-term use of the PPI and P-CAB. We performed endoscopic submucosal dissection of the lesions, with no recurrence or new lesions noted after discontinuation of the PPI and P-CAB.

Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab.

BACKGROUND: In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy. METHODS: The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves. RESULTS: During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001). CONCLUSIONS: Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer.

BACKGROUND: Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability. METHODS: The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists. RESULTS: ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6-99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2-94.5). CONCLUSIONS: ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN. TRIAL REGISTRATION: The UMIN Clinical Trials Registry Identification Number: 000004218.

[Evaluation of the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years].

Endoscopic treatments, including endoscopic mucosal resection or endoscopic submucosal dissection, are well accepted as standard treatments for early gastric cancers. However, there are few studies evaluating the safety and efficacy of this approach for early gastric cancers in patients aged over 80 years, and the post-treatment prognosis remains unclear. Here, we retrospectively analyzed the medical records and evaluated the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years (group A) compared with non-elderly patients aged 65-79 years (group B) and under 65 years (group C). In this study, we enrolled 53 patients (mean age, 82 years) in group A, 217 patients (mean age, 73 years) in group B, and 89 patients (mean age, 60 years) in group C who received endoscopic treatment at Kyoto University Hospital between 2001 and 2010. The incidence of treatment-related complications including aspiration pneumonia, bleeding, and perforation was 19% (10/53) in group A, 9.7% (21/217) in group B, and 6.7% (6/89) in group C, respectively. In particular, only the incidence of aspiration pneumonia was significantly higher in group A [11% (6/53) ] than in the other two groups [1.8% (4/217) in group B and 1.1% (1/89) in group C]. There was no significant difference in the curative resection rate and recurrence rate including metachronous lesions among the three groups. In group A, the median survival calculated using the Kaplan-Meier method was 8.0 years, and the 5-year survival rate was 73%. No gastric cancer-related deaths were observed in all groups. In conclusion, endoscopic treatment for early gastric cancers may contribute to an improvement in life expectancy, even among patients aged over 80 years, provided an experienced gastroenterologist selects the appropriate patients based on not only the endoscopic findings for the lesion but also the severity of any comorbidities. However, it is noteworthy that our elderly group aged over 80 years had a high risk of developing aspiration pneumonia.

The Distribution of Phosphatidylcholine Species in Superficial-Type Pharyngeal Carcinoma.

Objectives. Superficial-type pharyngeal squamous cell carcinoma (STPSCC) is defined as carcinoma in situ or microinvasive squamous cell carcinoma without invasion to the muscular layer. An exploration of the biological characteristics of STPSCC could uncover the invasion mechanism of this carcinoma. Phosphatidylcholine (PC) in combination with fatty acids is considered to play an important role in cell motility. Imaging mass spectrometry (IMS) is especially suitable for phospholipid analysis because this technique can distinguish even fatty acid compositions. Study Design. IMS analysis of frozen human specimens. Methods. IMS analysis was conducted to elucidate the distribution of PC species in STPSCC tissues. STPSCC tissue sections from five patients were analyzed, and we identified the signals that showed significant increases in the subepithelial invasive region relative to the superficial region. Results. Three kinds of PC species containing arachidonic acid, that is, PC (16:0/20:4), PC (18:1/20:4), and PC (18:0/20:4), were increased in the subepithelial invasive region. Conclusion. These results may be associated with the invasion mechanism of hypopharyngeal carcinoma.

The prospect of endoscopic submucosal dissection for early anal canal squamous cell carcinoma.

Squamous cell carcinoma (SCC) of the anal canal is seldom diagnosed at an early stage. Chemoradiation therapy is a standard in Europe and the United States, though in squamous cell carcinoma there is no evidence-based therapy. In Japan, endoscopic submucosal dissection (ESD) is the standard minimally invasive treatment for early stage cancer of the digestive tract, including the colorectum. Therefore, if the lesion is diagnosed at an early stage, ESD may be selected for anal canal lesions. We experienced two cases of early stage anal canal cancer in which the diagnosis and the extent of the lesions were confirmed using magnifying endoscopy with narrow-band imaging (NBI), as well as performing ESD. Pathological examination showed the resected specimen to be SCC in situ; the horizontal and vertical margins were free of tumor; and in one case there was no lymphovascular invasion. In the other case it showed the tumor was contained within the epithelium; horizontal and vertical margins were free of tumor; The follow-up period is not long enough to assert that ESD for anal canal squamous cell carcinoma may be an option of minimally invasive therapy. However, if there is a possibility of lymphatic invasion as in one of our cases, we need to give serious consideration to ESD for these lesions, and careful follow-up is necessary even if the lesion is in situ.

Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review.

Paraneoplastic neurological syndromes (PNSs) are rare nervous system dysfunctions in cancer patients, which are primarily observed with small-cell lung cancer, gynecological cancer, and thymoma. We herein present an uncommon case of PNS in an anti-Hu antibody-positive patient with human epidermal growth factor receptor (HER)-2-positive gastric cancer (GC), who developed limbic encephalitis and a worsening cognitive function. Trastuzumab-combined chemotherapy was initiated and appeared to be partially effective for controlling the neurological symptoms and tumor volume. Chemotherapy failure eventually led to uncontrollable neurological symptoms. This is the first case demonstrating that trastuzumab-combined chemotherapy may be effective for controlling neurological symptoms of PNS in HER2-positive GC patients.

Voice Outcome in Patients Treated With Endoscopic Laryngopharyngeal Surgery for Superficial Hypopharyngeal Cancer.

OBJECTIVES: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery that was developed to treat superficial larygo-pharyngeal cancer, in which a mucosal lesion is resected transorally while preserving deeper structures by subepithelial injection. The purpose of this retrospective study is to evaluate voice outcome in patients who underwent ELPS for superficial hypopharyngeal cancer. As important structures in producing voice, such as intrinsic laryngeal muscles, their fascia, and recurrent laryngeal nerve, are located in the medial side of the piriform sinus and the postcricoid region of the hypopharynx, we focused on patients with cancer lesions involving these regions. METHODS: From April 2010 to March 2011, 25 consecutive patients with superficial laryngopharyngeal cancer were treated with ELPS at Kyoto University Hospital. Among the 25 patients, 11 patients with cancer lesions on the medial side of the piriform sinus or the postcricoid area were studied. Preoperative and postoperative voice functions including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, soft phonation index (SPI), and noise-to-harmonic ratio (NHR), were compared retrospectively. RESULTS: Five of 11 cancer lesions had submucosal invasion and no lesion had invaded the muscular layer pathologically. T stage was classified as Tis in 5 cases, T1 in 4 cases, and T2 in 2 cases. All lesions involved the medial side of the piriform sinus and 2 also involved the postcricoid area. Vocal fold movement was normal in all cases after the surgery. Average preoperative and postoperative values for MPT, MFR, jitter, shimmer, SPI, and NHR, were 22.7 seconds and 23.4 seconds, 165 mL/sec and 150 mL/sec, 1.53% and 1.77%, 3.82% and 5.17%, 35.5 and 36.6, and 0.13% and 0.14%, respectively. There was no statistical difference between preoperative and postoperative data for all values examined. CONCLUSION: ELPS is useful in preserving voice function in the treatment of superficial hypopharyngeal cancer. Preserving the deeper structures including intrinsic muscles and their fascia may be important for preserving voice function as long as the lesions are superficial.

Endoscopic laryngo-pharyngeal surgery for superficial laryngo-pharyngeal cancer.

BACKGROUND AND STUDY AIMS: Narrow band imaging (NBI) combined with magnifying endoscopy enables us to detect superficial laryngo-pharyngeal cancers, which are difficult to detect by standard endoscopy. Endoscopic laryngo-pharyngeal surgery (ELPS) is a technique developed to treat such lesions and the purpose of this study is to evaluate the usefulness of ELPS for superficial laryngo-pharyngeal cancer. PATIENTS AND METHODS: Seventy five consecutive patients with 104 fresh superficial laryngo-pharyngeal cancers are included in this study. Under general anesthesia, a specially-designed curved laryngoscope was inserted to create a working space in the pharyngeal lumen. A magnifying endoscope was inserted transorally to visualize the field and a head & neck surgeon dissected the lesion using the combination of the orally-inserted curved grasping forceps and electrosurgical needle knife in both hands. The safely, functional outcomes, and oncologic outcomes of ELPS were evaluated retrospectively. RESULTS: Median operation time per lesion was 35 min. Post-operative bleeding occurred in 3 cases and temporal subcutaneous emphysema occurred in 10 cases. No vocal fold impairment occurred after surgery. The median fasting period was 2 days and all patients except one have a normal diet with no limitations. Local recurrence occurred in 1 case, and the 3-year overall survival rate and the 3-year disease specific survival rate was 90% and 100%, respectively. CONCLUSIONS: ELPS is a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, and enjoys the merit of both procedures. ELPS makes it possible to perform minimally-invasive surgery, preserving both the swallowing and phonation functions.

Transoral surgery for laryngo-pharyngeal cancer - The paradigm shift of the head and cancer treatment.

Transoral surgery is a less invasive treatment that is becoming a major strategy in the treatment of laryngo-pharyngeal cancer. It is a minimally invasive approach that has no skin incision and limits the extent of tissue dissection, disruption of speech and swallowing muscles, blood loss, damage to major neurovascular structures, and injury to normal tissue. Transoral approaches to the laryngo-pharynx, except for early glottis cancer, had been limited traditionally to tumors that can be observed directly and manipulated with standard instrumentation and lighting. Since the 1990s, transoral laser microsurgery (TLM) has been used as an organ preservation strategy with good oncological control and good functional results, although it has not been widely used because of its technical difficulty. Recently, transoral robotic surgery (TORS) is becoming popular as a new treatment modality for laryngo-pharyngeal cancer, and surgical robots are used widely in the world since United States FDA approval in 2009. In spite of the global spread of TORS, it has not been approved by the Japan FDA, which has led to the development of other low-cost transoral surgical techniques in Japan. Transoral videolaryngoscopic surgery (TOVS) was developed as a new transoral surgery system for laryngo-pharyngeal lesions to address the problems of TLM. In TOVS, a rigid endoscope is used to visualize the surgical field instead of a microscope and the advantages of TOVS include the wide operative field and working space achieved using the distending laryngoscope and videolaryngoscope. Also, with the spread of narrow band imaging (NBI), endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), which are widely used for superficial cancers in the gastrointestinal tract, have been applied for the superficial laryngo-pharyngeal cancer. Both EMR and ESD are performed mainly by gastroenterologists with a sharp dissector and magnifying endoscopy (ME)-NBI with minimal surgical margin. Endoscopic laryngo-pharyngeal surgery (ELPS) was developed to treat laryngo-pharyngeal superficial cancer by modifying the ESD procedure. The concept of ELPS is the same as that of ESD, however, the resection procedure is performed by a head and neck surgeon with both hands using a ME-NBI and rigid curved laryngo-pharyngoscope. These four procedures are low cost with similar oncological and functional outcomes to TORS. TORS may be less expensive than chemoradiotherapy, but the number of hospitals that can afford da Vinci surgical systems is limited. Even in the era of robotic surgery, these four procedures will be good options for laryngo-pharyngeal cancer.

Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer.

OBJECTIVES/HYPOTHESIS: To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME-NBI) is useful in predicting pathological depth of tumor invasion in laryngo-pharyngeal cancer. STUDY DESIGN: Retrospective study. METHODS: Preoperative endoscopy reports and postoperative pathological reports on 139 laryngo-pharyngeal cancer lesions were retrospectively reviewed, and the association between macroscopic findings in the lesions and the depth of tumor invasion was analyzed statistically. RESULTS: The ratios of lesions macroscopically classified as 0-I (superficial and protruding), 0-IIa (slightly elevated), 0-IIb (true flat), 0-IIc (slightly depressed), and 0-III (superficial and excavated) in the preoperative endoscopy reports were 3%, 25%, 71%, 1%, and 0%, respectively. Regarding the depth of tumor invasion in the postoperative pathological reports, the ratios of lesions classified as EP (carcinoma in situ), SEP (tumor invades subepithelial layer), and MP (tumor invades muscularis propria) were 73%, 26%, and 1%, respectively. The ratios of subepithelial invasion or muscular invasion in 0-I, 0-IIa, and 0-IIb were 100%, 54%, and 14%, respectively, and showed significant difference (P < 0.0001). Only one of 139 lesions invaded the muscular propria. CONCLUSIONS: This study is the first one to show that macroscopic findings by ME-NBI predict the depth of tumor invasion in superficial laryngo-pharyngeal cancer. It was indicated that there is a little chance of muscular invasion if the lesion is endoscopically diagnosed as 0-I or 0-II. A new T stage classification based on the depth of tumor invasion may be needed in order to adapt the classification to include transoral surgery. LEVEL OF EVIDENCE: 4.

Clinical outcome after endoscopic resection for superficial pharyngeal squamous cell carcinoma invading the subepithelial layer.

BACKGROUND AND STUDY AIMS: The curability of endoscopic resection for superficial pharyngeal squamous cell carcinoma (SPSCC) has not been fully elucidated, particularly for lesions invading the subepithelial layer, which carry the risk of metastasis. The aim of this study was to evaluate the curative potential of endoscopic resection for SPSCC invading the subepithelial layer. PATIENTS AND METHODS: From June 2002 to July 2010, 198 SPSCCs in 176 consecutive patients were treated by endoscopic resection at two tertiary referral centers. Selection criteria were initial endoscopic resection, histologically proven squamous cell carcinoma invading the subepithelial layer, no lymph node or distant metastasis before endoscopic resection, and no prior treatment for pharyngeal squamous cell carcinoma. Endoscopic resection was performed under general anesthesia. Long-term survival and clinical outcomes were retrospectively evaluated. RESULTS: Among 176 consecutive patients, 50 lesions in 47 patients (all male; median age 64 years) were histologically diagnosed from endoscopic resection specimens as having subepithelial invasion. Median tumor thickness was 1000 µm (range 200 - 10 000 µm). Six patients developed local recurrence (13 %; 95 % confidence interval [CI] 3.1 % - 22.4 %), and all were cured with organ-preserving intervention. After a median follow-up period of 71 months (range 27 - 116 months), one patient (2 %; 95 %CI 0 - 6.3 %) developed neck lymph node metastasis. A total of 14 patients (30 %) were followed for 5 years or more, and 5-year overall survival and disease-specific survival rates were 84.5 % (95 %CI 73 % - 96 %) and 100 %, respectively. CONCLUSIONS: Endoscopic resection has curative potential as a minimally invasive treatment option for SPSCC that invades the subepithelial layer.

Magnifying endoscopy with narrow band imaging to determine the extent of resection in transoral robotic surgery of oropharyngeal cancer.

Transoral robotic surgery (TORS) is a less invasive treatment that is becoming popular all over the world. One of the most important factors for achieving success in TORS is the ability to determine the extent of resection during the procedure as the extent of resection in the laryngopharynx not only affects oncological outcomes but also directly affects swallowing and voice functions. Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical technology that provides high-resolution images and is useful in detecting early superficial pharyngeal cancers, which are difficult to detect by standard endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been successfully treated by combining MB-NBI with TORS and MB-NBI was useful in determining the extent of resection. ME-NBI with TORS will make it possible to achieve a higher ratio of minimally invasive treatment in pharyngeal cancer.